Polymorphonuclear leukocytes (neutrophils) are specialized cytotoxic cells that provide host defense against bacteria, fungi and viruses. Recent evidence suggests that neutrophils also participate in cytotoxic reactions against neoplastic cells. In addition, neutrophils induce tissue injury in many immunologically mediated diseases. Neutrophil cytotoxicity involves several mechanisms which are independently controlled and regulated through cell membrane receptors. Lymphocytes produce humoral mediators that may regulate these cytotoxic mechanisms. We recently described a newly recognized T-lymphocyte product that inhibits the migration of human neutrophils (NIF-T). We purified NIF-T by antibody affinity chromatography and determined its subunit structure. We also demonstrated that human neutrophils have specific binding sites for NIF-T. NIF-T has now been purified to apparent homogeneity. This accomplishment provides us with a sensitive and specific screening system for the production of monoclonal antibodies to NIF-T. We will now use purified NIF-T to determine the effect of NIF-T on neutrophil cytotoxicity for infectious agents and neoplastic cells. We will also assess the role of NIF-T in mediating neutrophil-induced tissue injury in autoimmune diseases. Our specific goals are: (1)\to obtain monoclonal antibodies to NIF-T; (2)\to use the monoclonal antibodies to develop a radioimmunoassay for the detection of NIF-T; (3)\to use monoclonal antibodies to purify NIF-T to homogeneity by affinity chromatography; and (4)\to assess the effect of NIF-T on neutrophil function. Basic studies will include the effect of NIF-T on chemotaxis, phagocytosis, lysosomal enzyme release and superoxide anion production. Clinical studies will assess the effect of NIF-T on neutrophil cytotoxicity for bacteria, fungi, viruses and neoplastic cells.